HIFU has emerged as a precise, non-surgical, minimally-invasive treatment for benign and malignant tumors. At focal intensities (1000-10000 W/cm2) that are 4-5 orders of magnitude greater than that of diagnostic ultrasound (approximately 0.1 W/cm2), HIFU can be applied percutaneously to induce lesions (i.e., localized tissue necrosis) at a small, well defined region (approximately 1 mm) deep within tissue, while leaving intervening tissue between the HIFU transducer and the focal point substantially unharmed. Tissue necrosis is a result of tissue at the focal point of the HIFU beam being heated to over 70° C. in a very short period of time (generally less than one second). Tissue necrosis also results from cavitation activity, which causes tissue and cellular disorganization. HIFU is currently being used clinically for the treatment of prostate cancer and benign prostatic hyperplasia, as well as the treatment of malignant bone tumors and soft tissue sarcomas. Clinical trials are currently being conducted for HIFU treatment of breast fibroadenomas, and various stage-4 primary and metastatic cancerous tumors of the kidney and liver.
Therapeutic uses of HIFU have generally been directed at destroying undesired masses of tissue, to necrose tumors, coagulate bleeding, and address urological and gynecological disorders. Most references teach that one must use extreme care when using HIFU to treat tissue near a nerve, to avoid undesirably damaging the nerve. There are however, several medical conditions where it would be desirable to treat a nerve. For example, a temporary blocking of a nerve would prevent transmission of pain signals through that nerve, and could therefore be used for pain management. Temporary or permanent blockage by the nerve could also be used to treat spasticity.
Spasticity is a complication associated with disorders of the central nervous system (CNS), such as multiple sclerosis, cerebral palsy, stroke, and traumatic injury to the brain or spinal cord, and is displayed by uncontrollable muscle contractions. Spasticity due to trauma results from the generation of hyperactive nerve reflexes in pathways below the site of spinal cord or brain damage. It is estimated that over 500,000 individuals in the U.S. and over 12 million worldwide are affected by spasticity, many of whom suffer from severe spasticity, which includes violent and immobilizing spasms, despite paralysis in the lower limbs due to spinal cord injury or disease. Severe spasticity can also affect those with multiple sclerosis, traumatic brain injury, stroke, and cerebral palsy, among other CNS disorders. Many of these individuals retain voluntary function of the hyperactive nerve reflexes, but the interfering spasticity limits this function and compromises quality of life by causing pain and disrupting sleep.
The cause of spasticity is thought to involve hyperactivity of stretch reflexes. One proposed neuronal mechanism is that inhibitory portions of the reflex arc are impaired and thus, reflex muscle contractions may be unintentionally excited and proceed in a less controlled manner. Another proposed neuronal mechanism is that Ia afferents of the stretch reflex sprout new synapses on motoneurons in response to loss of normal supraspinal input due to a CNS disorder; as a result, the sprouted Ia afferents exert exaggerated synaptic excitation of motoneurons causing spasticity.
Mild or moderate spasticity can often be managed with physical methods (e.g., stretching, bracing) or oral spasmolytic medications (e.g., baclofen, tizanidine). However, these treatments are not adequate in the 25% to 50% of patients with severe spasticity. Treatments for severe spasticity include intramuscular blocks with botulinum toxin (BTX), which is often injected into 1 or 2 muscles with localized severe spasticity. For example, spasticity in ankle plantarflexor muscles causing clonus can be reduced with BTX injection into the gastrocnemius and soleus muscles. However, BTX has only modest effects in reducing spasticity. Only 1 or 2 large muscles can be injected because of concerns about systemic effects that could paralyze respiratory muscles, the duration of benefit is only 3-6 months, and repeated injections may be less effective because antibodies to BTX can develop.
Chemical nerve blocks with phenol or alcohol are also common treatments of severe spasticity. These chemical blocks can be applied to both peripheral nerves and spinal nerves to provide treatment of spasticity that is either localized to a specific muscle group or more widespread. The disadvantages to chemical nerve blocks include the risk of infection due to needle insertion, the difficulty in titration of the effect of treatment, and a risk (10 to 30%) of transient dysesthesias.
For very extreme cases of spasticity, patients often undergo peripheral surgery for cutting nerves or tendons, spinal cord surgery for cutting dorsal roots (dorsal rhizotomy) or cutting the spinal cord itself (i.e., longitudinal myelotomy). Other treatments of spinal nerve roots include intrathecal phenol and paravertebral alcohol neurolytic blocks. Paravertebral injections with alcohol carry the risk of infection and the risk of ascending myelopathy if the injected alcohol enters a dural root sleeve. Intrathecal phenol injections carry significant risks, such as the risk of disrupting bowel, bladder, and sexual function, the risk of infection, and the risk of ascending myelopathy because of migration of the phenol. Dorsal rhizotomy and lumbar myelotomy carry all of the risks associated with major surgery (i.e., risks associated with general anesthesia and the risk of infection). A less invasive, radio frequency rhizotomy uses thermo-coagulation of spinal nerves to control spasticity, although the risk of infection is still associated with this technique because the technique requires needle insertion.
Most current treatment options for severe spasticity are primarily used for patients with no preserved voluntary function, because these treatments (BTX, chemical nerve blocks, and the extreme case of nerve transection surgeries) have a non-selective effect on the local nerves and/or muscles. The result will be suppression of voluntary function in the treated region, either temporarily or permanently. Another treatment option, intrathecal baclofen infusion via a subcutaneous pump, has been used to treat patients who retain limited voluntary function. Such treatment (a continuous intrathecal infusion of the spasmolytic medication baclofen around the lumbar spinal cord) has been successful in reducing spastic contractions while preserving voluntary function, although the mechanism of its selectivity is not well understood. Despite its effectiveness, the invasiveness of the procedure and cost of the implantation procedure and the pump itself make other alternative procedures (such as nerve blocks and intramuscular blocks) more attractive for patients with no voluntary function.
Current treatments of spasticity can be classified as those that suppress voluntary function (intramuscular injections, nerve blocks, surgical treatments) and those that can retain voluntary function (stretching, oral medications, and intrathecal baclofen). Only stretching and oral medications are non-invasive treatments, and those treatments are ineffective for severe spasticity. Therefore, it would be desirable to provide a new, non-invasive treatment for severe spasticity. It would further be desirable to employ a non-invasive treatment that can achieve a relatively temporary partial conduction block, a relatively permanent partial conduction block, a relatively temporary complete conduction block, and a relatively permanent complete conduction block.
Severe chronic pain is a common clinical neurological condition. Such pain can be associated with some forms of cancer (particularly bone cancer), pain caused by peripheral nerve injury such as herpetic neuralgia, and some arthritis pain such as spinal facet arthropathies. Current treatments of pain include oral medications (e.g., morphine), local neurolytic alcohol injections, and thermo-coagulation of nerves. Similar to the treatments of spasticity, these methods are invasive, are often less effective than desired, and often have undesirable side effects. It would therefore be further desirable to provide a non-invasive method of treatment for sensory nerves in pain management.
Ultrasound has previously been used to treat less severe pain in physical therapy settings, in which the ultrasound beam is typically unfocused and of relatively low intensity compared to HIFU. The diffuse energy may act to soothe pain by providing heat to the area, acting no differently than a warm bath or massage. It would be desirable to provide a method for alleviating pain using HIFU by treating nerves with HIFU to achieve both thermal and mechanical interaction with nerves.